The purpose of this project is to determine the mechanisms of origin of the abnormal lipoprotein of cholestasis, commonly called LP-X, and the other atypical plasma lipoproteins present in this disorder. Both LP-X and the other atypical lipoproteins of humans with cholestasis were found to have similar counterparts in perfusates of livers from rats with experimental cholestasis (common bile duct ligation). Therefore, by studying the hepatic origin of plasma liproproteins in this experimental system we may be able to find regulatory mechanisms of normal and abnormal lipoprotein metabolism that are applicable to humans. The goals for the comming year are as follows: (1) I will continue to measure the rate of secretion of different apoproteins by perfused livers of cholestatic, normal and sham-operated control rats; (2) I will further characterize plasma and perfusate lipoproteins of cholestasis; (3) I will search for the origin of LP-X by testing the postulated pinocytotic route of vesicle transport by using various electron microscopic tracers.